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Article

Dental Implants Rehabilitation in Patients with Vitamin D3 Imbalance: A Randomized Controlled Trial

1
Department of Oral Surgery, Borovskiy Institute of Dentistry, FSAEI HE I.M.Sechenov First MSMU of MOH of Russia (Sechenovskiy University), Mojaiskii val 11, 119048 Moscow, Russia
2
Department of Operative Surgery and Topographic Anatomy, FSAEI HE I.M.Sechenov First MSMU of MOH of Russia (Sechenovskiy University), 119435 Moscow, Russia
3
Department of Radiologic Diagnostics and Radiologic Therapy, FSAEI HE I.M.Sechenov First MSMU of MOH of Russia (Sechenovskiy University), B.Pirogovskaya 6/2, 119992 Moscow, Russia
4
Department of Biomedical, Surgical, and Dental Science, Università degli Studi di Milano, Viale Pisa 10, 20146 Milan, Italy
5
IRCCS Istituto Ortopedico Galeazzi, 20157 Milan, Italy
6
Department of Prosthodontics, Geriatric Dentistry and Craniomandibular Disorders, Dental Materials and Biomaterial Research, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Aßmannshauser Str. 4–6, 14197 Berlin, Germany
7
Department of Sport Medicine and Medical Rehabilitation, FSAEI HE I.M.Sechenov First MSMU of MOH of Russia (Sechenovskiy University), 119435 Moscow, Russia
8
Moscow Center for Advanced Studies, 123592 Moscow, Russia
9
Medical Prophylaxis Faculty, FSAEI HE I.M.Sechenov First MSMU of MOH of Russia (Sechenovskiy University), St. Trubetskaya, 8, Bld. 2, 119991 Moscow, Russia
*
Author to whom correspondence should be addressed.
Appl. Sci. 2025, 15(17), 9490; https://doi.org/10.3390/app15179490
Submission received: 9 August 2025 / Revised: 26 August 2025 / Accepted: 27 August 2025 / Published: 29 August 2025

Abstract

Background: Vitamin D3 is an important factor for bone metabolism, and its deficiency may affect dental implantation results. Materials and methods: 384 patients with a diagnosis of tooth loss and vitamin D deficiency were examined and treated with dental implants. Vitamin D3 supplements were prescribed by the endocrinologist for all patients in the individual dose. The patients were divided into two equal study groups (n = 192) depending on the dental implantation period: Group 1—operation after blood serum vitamin D3 level normalization; group 2—before reaching the reference level of vitamin D3. Follow-up examinations were performed on the day of dental implantation, 7 days later, 1, 3, 6, and 12 months later, and every 1 year after treatment (up to 10 years). Implant stability and peri-implant tissue condition were assessed with clinical and X-ray diagnostics. Patients also visited an endocrinologist 2 months after the start of the treatment, then every 6 months. Results: The target vitamin D3 level (30–60 ng/mL) (p < 0.001) was achieved in all patients after treatment. At the control examinations, peri-implantitis was diagnosed in 10 patients (2.6%). It was detected in the group of patients with severe vitamin D deficiency and vitamin D deficiency—2 (25%) and 8 (3.4%) patients; respectively (p < 0.05). There was no significant difference between groups for risk of complications or bone quality after treatment. Conclusions: Timely screening of vitamin D3 levels and the appropriate treatment by an endocrinologist in young and middle-aged patients allow for achieving 97.4% dental implantation success for a ten-year period.

1. Introduction

Restoration of dental arches has been a pressing issue for many years. One of the most modern and actively used methods of treatment for patients with tooth loss during the last 30–40 years is osseointegrated implantology. As reported also in recent studies, due to the changing ecological environment and various man-made factors, the prevalence of inflammatory diseases affecting peri-implant hard and soft tissues may affect the long-term durability of implant-supported restorations [1,2,3]. This problem may be associated with concomitant diseases, including those affecting metabolic processes, and it is particularly relevant for patients with diagnosed osteopenia and osteoporosis [4]. Endocrinologists have previously noted a relationship between vitamin D3 deficiency and parathyroid hormone concentration, which, in turn, affects the state of mineral metabolism [5,6]. Vitamin D3 directly affects bone remodeling processes and calcium metabolism in the body by increasing calcium absorption in the intestine and reabsorption in the kidneys and reducing its excretion in the urine [7,8,9]. Besides that, vitamin D3 affects osteocalcin and osteopontin, which are markers of various stages of bone maturation and mineralization [10]. Cholecalciferol also affects osteoblasts and modulates immune responses, stimulates healing and compaction of soft tissues around the implant, and improves the resistance of the sulcus around the implant to bacterial infections [10,11,12]. These properties are very important during the formation of secondary implant stability. Vitamin D3 deficiency, in turn, is a widespread disease, affecting 18.3% out of more than 100 million subjects in the age range of 15–105 years [13].
This problem is relevant for both developed and developing countries around the world, since studies of the prevalence of vitamin D3 deficiency in world regions have found that the incidence of this pathology varies in the Middle East, Europe, and the United States from 20 to 90% [14,15,16]. Many studies showed that there is a correlation between vitamin D3 deficiency and the development of diseases such as diabetes, cardiovascular and renal pathologies, and autoimmune diseases [16,17,18,19,20,21]. In the last decade, a correlation between vitamin D3 deficiency and a “downgrade” of mineral metabolism has been increasingly identified in young and middle-aged patients not previously included in the risk group for osteoporosis (women over 50 years of age with established menopause). This may be due to the presence of gastrointestinal or urinary system diseases, as well as work and rest regimes (low insolation, long-term work in closed spaces, diet regime, and its composition) [22]. Osseointegration of dental implants depends on the bone’s ability to regenerate, so it is assumed that vitamin D3 deficiency reduces the healing and bone formation process around the implanted bone. Because of that, the risk of developing an unfavorable outcome of treatment of patients with partial edentulism with dental implants naturally increases. Meanwhile, timely provided therapy to the patient to correct the D3-deficient status promotes the integration of implants [16] and also allows increasing their five-year survival rate to 100%, regardless of the patient’s gender and age.
The aim of this study is to improve the effectiveness of rehabilitation of patients with tooth loss and mineral metabolism disorders due to vitamin D3 deficiency using an interdisciplinary approach to dental implantation. For such purpose, the differences in clinical and metabolic parameters, as well as implant survival, were evaluated by comparing groups of patients with pre-compensated vitamin D3 levels and ones treated at the time of implant placement.

2. Materials and Methods

The present randomized controlled clinical trial in parallel groups was conducted in accordance with the Helsinki Declaration and in coordination with the local ethics committee (Protocol No. 34-20 dated 9 December 2020). The registration of the study was carried out in the database ClinicalTrials.gov. The protocol number is NCT04841213. There were no important changes to the trial after it commenced. The reporting of the present trial follows the guidelines of the CONSORT statement.
All the patients were recruited in the Department of Oral Surgery of Borovskiy Institute of Dentistry, Sechenov University. A total of 450 patients were examined for a diagnosis of K08.1 tooth loss (Partial secondary adentia) on the background of vitamin D3 deficiency in the absence of any other systemic pathology and without a history of medicines affecting bone metabolism, such as antiresorptive therapy or bisphosphonates. Sixty-six patients were excluded from the study due to the presence of concomitant diseases during follow-up by an endocrinologist.
Inclusion criteria:
  • Written informed consent from the patient to participate in the study.
  • Age between 18 and 50 years old.
  • Diagnosis of tooth loss (K08.1-ICD-10) [23] and vitamin D3 deficiency, which was confirmed by a laboratory blood test.
  • Absence of severe somatic pathology.
Exclusion criteria:
  • Age less than 18 and more than 50 years.
  • Pregnant or breastfeeding.
  • Presence of concomitant conditions such as blood diseases, uncontrolled diabetes, immunodeficiency, tuberculosis, or malignancies.
Early withdrawal criteria:
  • Patient’s refusal to continue participation in the study.
  • Pregnancy.
  • Non-compliance with postoperative recommendations.
  • Change in residential address.
The complaints and history of life and illness were collected at the first visit; a clinical examination was also conducted, which included an extraoral and intraoral examination.
All patients underwent a standard laboratory test to determine their vitamin D3 levels.
The list of tests that each patient took before the operation:
Hematology (leukocytes, neutrophils, erythrocytes, platelets, lymphocytes, eosinophils, monocytes, hemoglobin, hematocrit);
Biochemistry (fasting glucose, ALT—Alanine aminotransferase; AST—Aspartate Aminotransferase; alkaline phosphatase; creatinine; total and direct bilirubin; albumin);
Coagulogram (prothrombin time, APTT—activated partial thromboplastin time; fibrinogen);
Hormones (total vitamin D3 (25-(OH) vitamin D), TSH—thyroid stimulating hormone; parathyroid hormone (PT);
Total blood calcium;
Optional- P1NP (total procollagen type 1 N-terminal propeptide), CTX (C-terminal telopeptide);
Blood test for HIV (human immunodeficiency viruses), syphilis, hepatitis B and C;
Daily excretion of calcium in urine.
When vitamin D3 deficiency was detected, patients were referred to an endocrinologist for further examination. Systemic vitamin D3 treatment included Aquadetrim (cholecalciferol in drops, one drop contains 500 International Units) in individual dosages depending on the patients’ results of laboratory tests and consisted of 10,000–15,000 International Units (IU) (Medana Pharma S.A., Poland, registration number PN014088/01 dated 21 June 2017) for the first 2 months; 2–5 drops orally with a spoonful of water depending on the severity of the deficiency after 2 months and reaching the reference level of vitamin D for the entire monitoring period.
In the presence of other concomitant conditions that could affect the results of dental implant treatment, patients received dental care to the extent required, but they were not included in the study group (n = 66).
Before the surgical intervention, a study was performed using standard methods of radiation diagnostics: cone beam computed tomography (CBCT) of the upper and lower jaw areas, including the maxillary sinuses. In difficult surgical cases, the production of templates (prosthetic or surgical) was used.
In case of insufficient bone volume, bone grafting procedures were planned and performed by using bone-plastic materials (hydroxyapatite-Bio-Oss, Histograft, and collagen membrane BioGide).
As a result, 384 patients were included in the study. They were randomly divided into two groups, with a 1:1 allocation ratio. There were 192 patients in each study group.
Intervention groups
Group 1 included 192 patients who underwent dental implantation after stabilization of vitamin D3 levels during treatment with an endocrinologist (blood test results reached > 30–60 ng/mL, or 75–150 nmol/L). Group 2 included 192 people with vitamin D3 deficiency in the blood (values were <30 ng/mL, or <75 nmol/L). They had dental implantation during treatment with an endocrinologist before vitamin D levels were stabilized.
Traditional two-stage dental implantation was performed according to surgical protocols of dental implantation systems (Straumann (Institute Straumann AG, Switzerland, registered in Russia 3 October 2017 No. FSZ 2010/06855), Astra Tech (Dentsply Implant Manufacturing GmbH, Germany, registered in Russia 27 September 2018 No. FSZ 2008/02570), Osstem (South Korea), and Alpha Bio (Alpha Bio Tec Ltd., Israel, registered in Russia on 26 April 2017 No. FSZ 2009/05582)) for different types of bone tissue and in different clinical conditions.
Follow-up examinations for groups 1 and 2 were conducted on the day of surgery, 7 days, 1, 3, 6, and 12 months, and every 1 year after treatment, under periodic patient monitoring (the minimum follow-up period was 1 year, and the maximum was 10 years). Sutures were removed on the 7th day after the installation of dental implants, and with additional use of bone-plastic materials or related operations—after 14 days. In addition, patients visited an endocrinologist 2 months after the beginning of the treatment, then once every 6 months.
The primary stability of the implant was assessed on the day of surgery using the Penguin RFA system with Implant Stability Quotient (Integration Diagnostics, Sweden, registered 29 December 2017 RZN No 2017/6664) based on resonance frequency analysis through the tip of the MulTipeg device. The data are displayed as a stability coefficient on a scale from 1 to 99. Secondary stability was assessed 3 months after surgery during the installation of the healing abutment and then in the other follow-up visits. The measurements were carried out using the Penguin RFA device. Also, on day 7 and after 12 months of the postoperative period, an assessment of the color and swelling of the soft tissues around the implant was performed. For patients who had undergone preliminary bone grafting, the checkup was carried out on days 10–14. The color of the peri-implant tissues was assessed on a scale of 0–1, with 0 being normal color and 1 being hyperemic. The soft tissue edema was also assessed on a scale of 0–2, with 0 indicating the absence of edema, 1 indicating moderate edema, and 2 indicating intense edema compared to nearby tissues.
After 12 months, at the follow-up examination, in addition to a clinical study, X-ray diagnostics (sighting images, OPG) were performed to assess the condition of peri-implant bone levels.

Sample Size

The number of patients included in the study was calculated as the average number of patients with a need for dental restoration in young and middle age based on statistical data from the Russian Dental Association (approximately 83%) and was equal to 194 patients, taking into account drop-out (alpha is 5%, power is 80%, post-hoc power is 90.8%)—a total of 384 patients for both groups. The null hypothesis was there is no difference in complication rate for two groups of patients: Group 1—patients with dental implant insertion after vitamin D blood serum normalization and group 2—patients with dental implant insertion in the process of treatment with vitamin D supplements before reaching reference blood serum level.
The method of block randomization, namely “envelopes”, was used: a doctor who was not involved in the study prepared numbered opaque packages that contained information about the method of intervention (dental implantation before vitamin D3 levels stabilized or after treatment with an endocrinologist) for patients who had their code in the non-personal data table; this scientist informed endocrinologists and surgeons only about the code of the patient. The doctors who recruited the participants for the study did not have access to information about the distribution of patients. An endocrinologist and a surgeon were blinded in the study. The endocrinologist did not know the patient’s distribution. The operator (surgeon) did not know whether the reference values of vitamin D had been reached or whether treatment with an endocrinologist had just begun. All doctors filled the results of examination and investigation in the documents of anonymized patients.
To analyze the research results, we performed statistical data processing in Excel (Windows 11, 2022, Microsoft, Redmond, WA, USA) and RStudio (free license), Python programming language (R version 4.2.2 (2022-10-31 ucrt)). In the study of quantitative features, the determination of averages, standard deviations, and medians was carried out. For primary outcomes (primary and secondary stability of dental implants), the comparison between the groups was carried out after checking the normality of the sample distribution (Shapiro–Wilkes test): two study groups for one period—the Mann–Whitney criterion (abnormal distribution) or the T-Student (normal distribution); two groups for both periods—ANOVA (normal distribution). For secondary outcomes (color and edema of peri-implant tissues for all periods of monitoring), the Kruskal–Wallis criterion (abnormal distribution) and ANOVA one-way and two-way were used (comparison of two groups and one group in dynamics). When comparing the frequency of occurrence of the trait, an analysis of 4 and 5 complete tables and the Pearson chi-square criterion was performed. The correlation between several factors was determined using the Pearson criterion, and the bond density was estimated using the Spearman criterion. The results were considered statistically significant with a confidence of more than 95% (p < 0.05).

3. Results

A total of 384 patients participated in this study (Figure 1). The age of the patients ranged from 25 to 50 years: 303 patients were aged 25–44 years (corresponding to the young group according to the WHO) (78.91%), and 81 were between 45 and 50 (corresponding to the middle-aged group according to the WHO) (21.09%). The average age was 39.8 ± 5.1 years. A total of 144 (37.5%) men participated in the study, among whom 67 (22.11%) were young and 77 (95.06%) were middle-aged according to WHO. There were 240 (62.5%) women, including 236 (77.89%) aged 25 to 44 years and 4 (4.94%) aged 45 to 50 years (p > 0.05).
In both study groups, the number of patients was similar, and there were no significant differences in their ages (p > 0.05).
All patients underwent dental implantation after additional tests, including the determination of vitamin D levels (vitamin D levels < 30 ng/mL or <75 nmol/L were considered deficient).
According to the results of the preoperative laboratory tests, there were no abnormalities in hematology and biochemical blood tests, including mineral elements. The blood calcium level was within the normal range of 2.20–2.65 mmol/L, including after correction of its level with blood albumin.
When analyzing the hormonal status in all patients, the concentrations of thyroid-stimulating hormone and parathyroid hormone were also within the reference values: 0.4–4 mEd/L (according to Abbot technology) and 2–9.4 pmol/L (according to Abbot technology).
The analysis of vitamin D3 (25(OH-D, cholecalciferol) revealed a decrease in target values in all patients to one degree or another:
<10 ng/mL (severe deficiency)—8 (2.1%) patients;
<20 ng/mL (deficiency)—232 (60.4%) patients;
20–30 ng/mL (insufficiency)—144 (37.5%) patients.
After drug correction with vitamin D3 in a prescribed individual dose by an endocrinologist, all patients achieved target levels of vitamin D3 between 30 and 60 ng/mL, followed by constant intake of the drug in a dose of 1000 to 2000 IU. The levels of vitamin D3, depending on the study group, and their changes as a result of treatment, are presented in Table 1 [24].
When analyzing markers of osteogenesis before and after treatment, the study revealed no deviations from the reference values (P1NP—8–80 ng/mL; CTX < 0.573 ng/mL) (p > 0.05), although there was a slight significant decrease in indicators after treatment compared with baseline (Table 2).
The level of calcium in the blood of patients did not exceed the reference values when measured as total plasma calcium or when recalculated for albumin. However, the level of albumin was slightly lower by an average of 0.1 mmol/L, although this difference was not statistically significant (Table 3).
The stability of dental implants on the day of installation ranged from 30 to 40 N/cm2. The secondary stability was 40 ± 4.5 N/cm2.
During follow-up examinations after 7 days, 1, 3, 6, and 12 months, the majority of patients (374 patients—97.4%) did not have any complaints or signs of inflammation, as well as soft or bone tissue recessions in the area of the installed dental implants. On day 7, no edema or hyperemia was detected in any patient during external and intraoral examination.
Implant Stability Quotient for patients of both groups during insertion of dental implants varied between 82 and 86 (group 1 = 84 ± 1.4 (84), group 2 = 83.8 ± 1.4 (84), p > 0.05); during prosthetic insertion it varied between 86 and 90 (group 1 = 87.8 ± 1.4 (87), group 2 = 87.5 ± 1.4 (87), p > 0.05)
According to X-ray studies, there was no progressive bone loss in either group during the year, and dental implants remained stable.
During CBCT of the jaws in patients, in the study and assessment of the optical density of the area of future dental implantation, the predominance of bone tissue types D3 (350–850 Hu) in the upper jaw and D2 (850–1350 Hu) in the lower jaw. In rare cases, with prolonged absence of teeth (at least 1 year), type D1 (>1350 Hu) on the lower jaw.
Thirty patients were randomly selected and underwent CBCT of the jaw in the area of the installed implants after 3 months. The average values of the optical density of the jaws in the area of tooth loss in dynamics are shown in Table 4.
When conducting a control X-ray examination 1 year after the installation of dental implants, no marginal or apical bone resorption was detected in the area of the installed dental implants.
In the majority of patients with operations, good osseointegration of dental implants was shown with no complaints in the postoperative period during the entire follow-up period (from 1 year to 10 years).
The development of peri-implantitis was noted in 10 patients (2.6%). There was no significant difference in complication rate for both common groups (group 1—patients with dental implant insertion after vitamin D blood serum normalization and group 2—patients with dental implant insertion in the process of treatment with vitamin D supplements before reaching reference blood serum level). Although, all cases of peri-implantitis were detected in the group of patients with severe vitamin D deficiency and deficiency of vitamin D—2 (25%) and 8 (3.4%) cases; respectively (p = 0.04, p < 0.05). The treatment of patients with peri-implantitis was carried out according to the methods developed by us [25].

4. Discussion

Nowadays, edentulism is a widespread disease importantly affecting the patients’ quality of life. Dental implantation is being successfully used for the treatment of this condition, and one of the key criteria of successful implantation is good osseointegration of the dental implant into the jaw bone. Osseointegration can be influenced by many factors, one of which [26], for example, is the bone density in the area of the operation [27,28]. Disturbances in mineral metabolism may facilitate the development of diseases that can affect the density of jaw bone [22]. One of the reasons for these disorders is vitamin D deficiency, which leads to a decrease in the patients’ bone density. A decrease in bone mineral density (BMD) causes deterioration of osseointegration of placed dental implants [29,30,31]. It is known that the influence of vitamin D3 on bone and osseointegration is still a subject of discussion between clinicians. In several studies, the effect of vitamin D3 on osseointegration is assessed using biochemical blood tests: according to their results, on average, a higher level of vitamin D3 before implantation corresponded to less bone loss and a better process of osseointegration of the implant [32,33].
Another way to assess the effect of vitamin D3 is the analysis of changes in its concentration in the blood serum with systematic intake of food supplements [34,35]. However, these studies have their drawbacks. First of all, the effect of vitamin supplements was studied with its initial deficiency. Also, subjects in clinical studies spent different amounts of time in daylight, despite daily intake of supplements. Some studies claim that the effect of taking vitamin D3 doses in organisms with sufficient or insufficient levels of cholecalciferol differs from the effect on organisms with vitamin D3 deficiency. Thus, Burt L.A. et al. report that additional intake of high doses of vitamin D3 reduces bone mineral density [36]. At the same time, determining the exact required daily dose of cholecalciferol is quite difficult. There are still no general recommendations for the optimal intake of this vitamin, and its prescriptions are personalized [37]. In our study, we found in patients with vitamin D deficiency an increase in optical bone density after appropriate treatment with cholecalciferol in individual dosages prescribed by endocrinologists for both study groups (p < 0.05).
Nastri L et al. and other authors noted [12,38] that vitamin D also stimulates healing and compaction of soft tissues around the dental implant and improves resistance to bacterial infections of the sulcus around the implant, which is very important for the secondary stability of dental implants. Several authors have different points of view. Alsulaimani L. et al. concluded that in the clinical cases they examined, a direct connection between these indicators is difficult to identify, and the early loss of the dental implant was caused by other factors (smoking, improper bone restoration, and low level of gingiva keratinization) than by low levels of vitamin D3 in the blood serum of patients [26]. We found that a higher percentage of such complications as peri-implantitis was in the patients with severe deficiency of vitamin D in comparison with other deficiency types (p < 0.05).
Before conducting our work, we surveyed oral surgeons and prosthetic dentists to determine their awareness regarding the potential influence of vitamin D on the osseointegration of dental implants (the survey was anonymous and contained an information letter about the study process and results use): at the surgical stage of treatment, peri-implantitis was the most common complication; at the prosthetic stage, mucositis. The frequency of dental implant loss was comparable among specialists of both profiles. Among prosthetic dentists and oral surgeons, there was a rare prescription of laboratory examination of patients and a low frequency of referring patients, even with identified disorders of mineral metabolism, to an endocrinologist and other specialists (up to 35%). Among surgical methods for the treatment of peri-implantitis, regenerative and resection techniques were found to be predominant, with a lower incidence of dental implant loss [26]. Currently, modern research confirms that the prevalence of peri-implantitis is higher than previously thought. Thus, according to previous studies, successful implantations had a success rate of 91.6%, and during 10 years of follow-up, 7% of patients developed peri-implantitis. Other studies reported postoperative complications in 10–15% of cases after surgery [39,40]. The survey demonstrated the importance of the study, as recent observations show that in the first 10 years after implantation, the incidence of peri-implantitis ranges from 1% to 47% [41], while according to some data, peri-implantitis can occur in 85% of cases [42], especially in the case of concomitant pathologies and bad habits, such as both smoking and poor oral hygiene [25,43,44]. In our study, the total complication rate was 2.6%, but if vitamin D deficiency type were to be considered, then this rate would be significantly higher for severe deficiency—25% of cases.
In addition to clinical examination, radiation and other physical examination methods are used to assess the condition of bone tissue around dental implants. For example, Kwiatek et al. [30] used conventional two-dimensional (2D) radiography to check the osseointegration of the implant and assess changes in the level of the alveolar ridge after surgery. In addition, they used the ISQ (Implant Stability Quotient) measurement to assess the stability of the implant due to osseointegration. Cone beam computed tomography has a higher resolution than computed tomography used for patients and is capable of measuring bone mineral density, the structure of which can be determined by the characteristics of trabeculae and their connectivity. This allows for a much more accurate assessment of the bone and the boundary between the bone and the implant. In our study, the radiation diagnostics of the area of tooth loss and the subsequent installation of dental implants showed an increase in the optical density of bone tissue 3 months after the start of treatment with vitamin D3 according to cone beam computed tomography.
The results of 75% of the studies reviewed in the scientific paper by Werny et al. showed that the systemic intake of vitamin D supplements enhances the formation of new bone around dental implants [29]. The systematic review included two clinical trials and three case reports, and the latter only included men. Dental implants made of titanium or titanium-zircon were installed in all scientific papers [30,31,45,46,47]. The patients were followed up for between 12 weeks and seven months, depending on the study. One study aimed to investigate the effect of vitamin D supplementation on bone changes at the site of dental implant during osseointegration [30]. Another study was devoted to the search for a relationship between early implant rejection and vitamin D levels in blood serum [31]. Clinical reports described the effect of vitamin D supplementation on osseointegration in patients with diagnosed vitamin D deficiency [45,46], as well as with end-stage renal failure [48]. Two clinical reports described implant failure in three patients with vitamin D deficiency [45,46]. Mangano et al. found that patients with low serum vitamin D3 levels were at greater risk of early implant rejection [31]. Kwiatek et al. found that vitamin D supplements influenced bone changes around dental implants [30]. Fretwurst et al. also report two cases of successful treatment using dental implants [46]. All these studies involved patients with diagnosed vitamin D deficiency and one or two episodes of dental implant loss. Nevertheless, vitamin D supplementation has been successful in treatment [45]. Flanagan et al. describe one case of successful dental implant treatment for a patient with end-stage renal failure who was taking vitamin D supplements in addition to other medications [47]. Opposite to these studies, Pimentel et al. did not find a significant difference in the formation of new bone or bone-implant contact in patients with systematic vitamin D supplementation [10]. Patients with normal or insufficient vitamin D levels had a lower effect of taking vitamin D supplements than patients with deficiency [48]. In healthy patients, on the contrary, high doses of vitamin D could lead to a decrease in bone mineral density [37]. In our study, the individual dosage of vitamin D allowed for better bone quality around dental implants and decreased the possible risk of implant failure for patients with vitamin D deficiency.
Due to the limited number of studies conducted, the results provide only weak evidence of improved osseointegration due to vitamin D supplementation in humans. Clinical cases [45,46,47] that have studied the effect of vitamin D on osseointegration have a high risk of displacement. In particular, the effect of vitamin D supplementation on osseointegration in patients with diseases such as diabetes, osteoporosis, vitamin D deficiency, and kidney disease remains widely unknown. In our study, the good result possibly was reached also due to the absence of severe comorbidity, which could affect bone metabolism.
In the work of Werny JG et al., it was noted that patients with low levels of vitamin D in the blood serum have a higher tendency for early loss of dental implants. However, vitamin D supplementation revealed a beneficial effect on bone: osseointegration was successful [36]. These results are consistent with our research, although the null hypothesis was not rejected. Timely laboratory diagnosis and subsequent treatment of patients with vitamin D3 deficiency by an endocrinologist before or during implantation provide favorable outcomes, namely, improving the osseointegration of implants (follow-up periods ranged from 1 year to 10 years).

Study Limitations

Our study was limited by the uneven distribution of patients across age groups and gender within these groups. Patients in the 18–44-year-old group accounted for 78.91% of the total number of patients who took part in the study. Female patients predominated in the younger age group. They constituted 77.88% of the total number of patients, which is 15.38% higher than the average value of the ratio between the genders in both groups. In the older age group, on the contrary, male patients prevailed (95.06% with an average value of 37.5%). A three-month CBCT follow-up after dental implantation was not performed in all patients because the true optical density of the bone in the area of the installed dental implant and the presence of bone next to it were not determined due to background distortions and artifacts.

5. Conclusions

A deficiency of vitamin D3 can lead to the development of dental implantation complications, such as peri-implantitis, which will require additional treatment measures to stop the inflammatory process and save the implant. In our study, it was found that the peri-implantitis rate is significantly higher in patients with severe vitamin D deficiency and equals 25% of cases. Radiological diagnostic methods in young and middle-aged patients with a decrease in the level of vitamin D3 could have diagnostic value for early diagnostics of developing skeleton osteopenia, which could affect the success of dental treatment. The results of our study showed a decrease in the concentration of vitamin D3 to at least below 20 ng/mmol in young and middle-aged patients with tooth loss in the absence of comorbidity affecting bone metabolism. This condition could be corrected within several months of taking vitamin D3 in an individual dosage as prescribed by an endocrinologist. Our approach included the early screening of vitamin D3 levels and the appointment of appropriate treatment by an endocrinologist in young and middle-aged patients with vitamin D deficiency. This led to a 97.4% success rate in dental implantation over a 10-year follow-up, although vitamin D3 levels below 10 ng/mL in young and middle-aged patients may increase the risk of dental implant loss.

Author Contributions

Conceptualization, E.D. and S.C.; methodology, S.T. (Silvio Taschieri); software, E.K.; validation, V.Z., A.B. and N.Z.; formal analysis, S.B.; investigation, E.D.; resources, S.T. (Svetlana Tarasenko); data curation, A.U.; writing—original draft preparation, M.S., Y.Z. and M.K.; writing—review and editing, O.K.; visualization, E.K.; supervision, S.T. (Svetlana Tarasenko); project administration, O.K. and S.B.; funding acquisition, S.C. and S.T. (Silvio Taschieri) All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Sechenov University (Protocol No. 34-20 dated 9 December 2020).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The data presented in this study are available on request from the corresponding author due to requirements of the Local Ethical Committee.

Acknowledgments

We would like to thank Sechenov University for the opportunity to perform this study.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. Flowchart of the study.
Figure 1. Flowchart of the study.
Applsci 15 09490 g001
Table 1. Vitamin D3 values depending on the study group and its changes.
Table 1. Vitamin D3 values depending on the study group and its changes.
PeriodGroup 1—Setting the DI Before the Reference Values of Vitamin D3 are Reached
(n = 192)
Vitamin D3, ng/mL
Me ± m
Median
Min–Max
Group 2—Setting a Diet After Reaching the Target Values of Vitamin D3
(n = 192)
Vitamin D3, ng/mL
Me ± m
Median
Min–Max
p
(The Mann-Whitney Criterion)
Before treatment18.62 ± 5.2
18
11.53–29.3
18.15 ± 4.9
17.95
8–28.4
>0.05
After 3 months43.5 ± 8.3
42.75
31–62.3
43.3 ± 7.8
43.65
31.6–60.2
>0.05
p
(The Wilcoxon criterion)
<0.001<0.001
Table 2. Assessment of the level of osteogenesis markers in dynamics.
Table 2. Assessment of the level of osteogenesis markers in dynamics.
MarkerBefore Vitamin D Treatment
M ± m
The Median
After Vitamin D Treatment
M ± m
The Median
p
P1NP, ng/mL39.7 ± 7.3
41
36.1 ± 7
37
0.03
(p < 0.05)
CTX, ng/mL0.295 ± 0.12
0.3
0.275 ± 0.09
0.29
0.003
(p < 0.05)
Table 3. Recalculation of calcium in blood plasma with albumin (n = 384).
Table 3. Recalculation of calcium in blood plasma with albumin (n = 384).
IndicatorBefore Vitamin D Treatment
M ± m
The Median
p
Albumin, g/L45.6 ± 1.8
45.5
-
Calcium, mmol/L2.38 ± 0.06
2.38
-

p < 0.001
(p < 0.05)
Total calcium adjusted, mmol/L2.27 ± 0.1
2.28
Table 4. Optical density of jaw bone in the area of tooth loss at the planning stage of dental implantation and 3 months after the installation of dental implants.
Table 4. Optical density of jaw bone in the area of tooth loss at the planning stage of dental implantation and 3 months after the installation of dental implants.
PeriodGroup 1—Setting the DI Before the Reference Values of Vitamin D3 are Reached
(n = 15)
Optical Density, Hu
Me ± m
Median
Min–Max
Group 2—Setting the Diet After Reaching the Target Values of Vitamin D3
(n = 15)
Optical Density, Hu
Me ± m
Median
Min–Max
p
(The Mann-Whitney Criterion)
Before treatment744 ± 119
759
540–950
797 ± 88
787
594–925
>0.05
After 3 months918.5 ± 45
913.5
854–1030
917.5 ± 49
906
824–999
>0.05
p
(The Wilcoxon criterion)
<0.001<0.001
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Diachkova, E.; Skachkova, M.; Zhilkov, Y.; Kerimov, M.; Tarasenko, S.; Babkova, A.; Zhukova, N.; Bokareva, S.; Taschieri, S.; Unkovskiy, A.; et al. Dental Implants Rehabilitation in Patients with Vitamin D3 Imbalance: A Randomized Controlled Trial. Appl. Sci. 2025, 15, 9490. https://doi.org/10.3390/app15179490

AMA Style

Diachkova E, Skachkova M, Zhilkov Y, Kerimov M, Tarasenko S, Babkova A, Zhukova N, Bokareva S, Taschieri S, Unkovskiy A, et al. Dental Implants Rehabilitation in Patients with Vitamin D3 Imbalance: A Randomized Controlled Trial. Applied Sciences. 2025; 15(17):9490. https://doi.org/10.3390/app15179490

Chicago/Turabian Style

Diachkova, Ekaterina, Marina Skachkova, Yuryi Zhilkov, Magamed Kerimov, Svetlana Tarasenko, Anna Babkova, Natalia Zhukova, Svetlana Bokareva, Silvio Taschieri, Alexey Unkovskiy, and et al. 2025. "Dental Implants Rehabilitation in Patients with Vitamin D3 Imbalance: A Randomized Controlled Trial" Applied Sciences 15, no. 17: 9490. https://doi.org/10.3390/app15179490

APA Style

Diachkova, E., Skachkova, M., Zhilkov, Y., Kerimov, M., Tarasenko, S., Babkova, A., Zhukova, N., Bokareva, S., Taschieri, S., Unkovskiy, A., Kytko, O., Zaborova, V., Kytko, E., & Corbella, S. (2025). Dental Implants Rehabilitation in Patients with Vitamin D3 Imbalance: A Randomized Controlled Trial. Applied Sciences, 15(17), 9490. https://doi.org/10.3390/app15179490

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